Project Summary The broad long term goal of this research program is to reduce or eliminate deafness by developing sustained release intracochlear drug delivery systems. The goal of this project is to develop a steroid eluting cochlear implant. Currently, cochlear implantation leads to loss of residual hearing and the procedure is therefore reserved for the profoundly deaf. Inflammatory events at insertion are thought to contribute to this loss, and intracochlear steroids have demonstrated the potential to reduce inflammation and preserve residual hearing. The potential for implanting cochlear devices into people with residual hearing expands the world market to 278 million people suffering from moderate to profound hearing loss. In Phase 1 we formulated sustained release delivery systems for fluticasone, tested in vitro release, and confirmed sustained release and safety in an animal model. We furthermore formulated prototype cochlear implants releasing fluticasone, and have laid the basis for further commercialization with a corporate partner: Cochlear Corporation, the market leader in the field. In this Phase 2 work we propose to develop an inner ear delivery system for the steroid fluticasone to be used in cochlear implantation, and to test this formulation in an animal model of insertion trauma. The specific aims of this proposal are to 1, manufacture steroid eluting cochlear implants;2, confirm the in vitro release characteristics of these implants;and 3, test the in vivo efficacy of these implants after insertion into the inner ear of the guinea pig in a trauma insertion model. We have an understanding with Cochlear Corporation: when we demonstrate efficacy in an animal model they will license our technology. They have committed the donation of implants and technical expertise in the manufacturing of their system to this project. The team of investigators is expert in polymer chemistry, pharmacokinetics, drug development intracochlear pharmacokinetics and clinical otolaryngology. We have experience in all aspects of the drug development process, from concept to approval and marketing. PUBLIC HEALTH RELEVANCE: Project Narrative Cochlear implants are medical devices that electrically stimulate the auditory nerve fibers of the inner ear of patients who are profoundly deaf giving them a sensation of sound. Historically, cochlear implants were used for patients who had no hearing within the ear. Cochlear implants that elute steroids have the potential to reduce the loss of hearing from the traumatic insertion of the implant. This greatly expands the number of people who could benefit from obtaining a cochlear implant from those with profound hearing loss to those with moderate hearing loss. We have the technology and the expertise to develop steroid eluting cochlear implants.